The objectives of the proposed research are to provide new knowledge and understanding of developmental pharmacology and developmental physiology of the heart in the neonatal and young animal and child. Postnatal changes in myocardial contractile function, development of the cardiac sympathetic nervous system, and myocardial contractile responses to pharmacologic agents will be assessed in isolated papillary muscles and isolated atrial preparations from newborn and adult experimental animals and man. Responses of isolated myocardial preparations to changes in muscle length, changes in rate of stimulation, and paired electrical stimulation will be used to define the postnatal development of myocardial contractile function. These physiological investigations will be correlated with microscopic and biochemical studies on energy utilization to determine possible subcellular mechanisms responsible for postnatal changes in cardiac function. The postnatal development of the cardiac sympathetic nervous system will be examined by measuring changes in myocardial contractile function produced by beta adrenergic stimulants, beta adrenergic blocking drugs and agents which interfere with adrenergic neuronal function. In addition, age-related differences in endogenous catecholamine stores will be determined by fluorescence microscopy. Developmental pharmacologic studies of the heart will be performed by measuring age-related differences in myocardial contractile responses produced by various positive and negative inotropic agents.